Experimental systems have been developed which allow the determination of quantitative endpoints in normal tissues and in tumors in mice. These systems are employed in a search for methods which yield improved therapeutic ratios in experimental radiotherapy. The measurements of a normal tissue damage being applied include pulmonary, esophageal, renal and brain lethality as well as intestninal crypt cell survival assays and the grading of skin reactions. Tumor endpoints include five experimental mouse tumors: EMT 6/SF, Line 1, RIF, SQ 1 and CC 38. These tumors are treated as solid tumors in the flank or thigh and as pulmonary micro or macro colonies. Endpoints include regrowth, tumor control and cell survival measured in vitro after treatment in vivo. The radiation doses for damage to normal tissue and for a given level of cell kill in tumors with or without modifying agents including radiosensitizers, radioprotectors, low dose rate and high LET radiations are being compared in order to determine the therapeutic ratio.